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77 - Endothelial Cell Integrins
- from PART II - ENDOTHELIAL CELL AS INPUT-OUTPUT DEVICE
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- By Joseph H. McCarty, M.D. Anderson Cancer Center, Houston Texas, Richard O. Hynes, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge
- Edited by William C. Aird, Harvard University, Massachusetts
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- Book:
- Endothelial Biomedicine
- Published online:
- 04 May 2010
- Print publication:
- 03 September 2007, pp 707-713
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- Chapter
- Export citation
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Summary
The extracellular matrix (ECM) is an insoluble network of proteins that provides structural support to multicellular tissues and regulates a variety of cell behaviors. Most metazoan cells express transmembrane proteins, known as integrins, which serve as receptors for many ECM protein ligands (1). Integrins connect the extracellular environment to the intracellular cytoskeleton, and also regulate the signal transduction cascades leading to gene regulatory events. Integrin-mediated adhesion and signaling are essential for the proper formation of most tissues, and they play particularly important roles in vascular development and homeostasis (2).
HISTORY OF INTEGRINS
The discovery of integrins centered around efforts to identify a cell surface receptor for the fibrillar ECM protein fibronectin (FN) (3,4). Biochemical purification of the FN receptor revealed a complex of two proteins of differing molecular weights (5). Subsequent cloning and sequencing of cDNAs encoding components of the FN receptor complex identified two transmembrane proteins, named integrins for their postulated role in linking the ECM to the intracellular cytoskeleton. Soon thereafter, several investigators working in areas ranging from human immunology to fly genetics published the cDNA sequences encoding other transmembrane proteins with striking homologies to the FN receptor (3). Thus, it was realized that integrins represented a multigene family with adhesive functions on diverse cell types. We now know that integrins are heterodimeric proteins consisting of two noncovalently associated subunits, termed α and β. Most integrins recognize multiple ECM ligands, and many ECM proteins can bind to more than one integrin receptor. Integrins and their various ECM ligands play essential roles in virtually every aspect of physiological and pathological blood vessel function.